USP53 plays an antitumor role in hepatocellular carcinoma through deubiquitination of cytochrome c

Ye Yao; Weijie Ma; Yonghua Guo; Yingyi Liu; Peng Xia; Xiaoling Wu; Yiran Chen; Kunlei Wang; Chengjie Mei; Ganggang Wang; Xiaomian Li; Zhonglin Zhang; Xi Chen; Yufeng Yuan

doi:10.1038/s41389-022-00404-8

USP53 plays an antitumor role in hepatocellular carcinoma through deubiquitination of cytochrome c

Oncogenesis. 2022 Jun 2;11(1):31. doi: 10.1038/s41389-022-00404-8.

Authors

Ye Yao^#^{1

2}, Weijie Ma^#^{1

2}, Yonghua Guo^#^{1

2}, Yingyi Liu^{1

2}, Peng Xia^{1

2}, Xiaoling Wu^{1

2}, Yiran Chen^{1

2}, Kunlei Wang^{1

2}, Chengjie Mei^{1

2}, Ganggang Wang^{1

2}, Xiaomian Li^{1

2}, Zhonglin Zhang^{1

2}, Xi Chen^{3

4}, Yufeng Yuan^{5

6}

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
² Minimally invasive treatment center of hepatobiliary and pancreatic diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, P. R. China.
³ Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. [email protected].
⁴ Minimally invasive treatment center of hepatobiliary and pancreatic diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, P. R. China. [email protected].
⁵ Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. [email protected].
⁶ Minimally invasive treatment center of hepatobiliary and pancreatic diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, P. R. China. [email protected].

^# Contributed equally.

Abstract

Despite of advances in treatment options, hepatocellular carcinoma (HCC) remains nearly incurable and has been recognized as the third leading cause of cancer-related deaths worldwide. As a deubiquitinating enzyme, the antitumor effect of ubiquitin-specific peptidase 53 (USP53) has been demonstrated on few malignancies. In this study, we investigated the potential antitumor role of USP53 in HCC. The results showed that USP53 was downregulated in HCC tissues as well as in HCC cell lines using both in silico data as well as patient samples. Furthermore, the ectopic expression of USP53 inhibited the proliferation, migration and invasion, and induced the apoptosis of HCC cells. Co-immunoprecipitation (CO-IP) assay and mass spectrometry (MS) combined with the gene set enrichment analysis (GSEA) identified cytochrome c (CYCS) as an interacting partner of USP53. USP53 overexpression increased the stability of CYCS in HCC cells following cycloheximide treatment. Finally, the overexpression of CYCS compensated for the decreased apoptotic rates in cells with USP53 knocked down, suggesting that USP53 induced the apoptosis in HCC cells through the deubiquitination of CYCS. To summarize, we identified USP53 as a tumor suppressor as well as a therapeutic target in HCC, providing novel insights into its pivotal role in cell apoptosis.